Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump α2 subunit (Atpla2)-deficient mice

Keiko Ikeda, Tatsushi Onaka, Makoto Yamakado, Junichi Nakai, Tomo O. Ishikawa, Makoto M. Taketo, Kiyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)

Abstract

The sodium pump is the enzyme responsible for the maintenance of Na+ and K+ gradients across the cell membrane. Four isoforms of the catalytic α subunit have been identified, but their individual roles remain essentially unknown. To investigate the necessary functions of the α2 subunit in vivo, we generated and analyzed mice defective in the α2 subunit gene. Mice homozygous for the α2 mutation died just after birth and displayed selective neuronal apoptosis in the amygdala and piriform cortex. In these regions, high expression of c-Fos before apoptosis indicated neural hyperactivity, and re-uptake of glutamic acid and GABA into P2 fraction containing crude synaptosome was impaired. These results indicate that the α2 subunit plays a critical role regulating neural activity in the developing amygdala and piriform cortex. Further supporting a role of the α2 subunit in the function of the amygdala, heterozygous adult mice showed augmented fear/anxiety behaviors and enhanced neuronal activity in the amygdala and piriform cortex after conditioned fear stimuli.

Original languageEnglish
Pages (from-to)4667-4676
Number of pages10
JournalJournal of Neuroscience
Volume23
Issue number11
DOIs
Publication statusPublished - 2003 Jun 1
Externally publishedYes

Keywords

  • Amygdala
  • Fear-anxiety behavior
  • Knock-out mice
  • Na,K-ATPase
  • Neurotransmitter uptake
  • Piriform cortex

ASJC Scopus subject areas

  • Neuroscience(all)

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